title: Monocyte chemoattractant protein-1-deficiency results in altered blood-brain barrier breakdown after experimental stroke.
abstract: OBJECTIVE
  Stroke-induced blood-brain barrier (BBB)-disruption can contribute to further progression of cerebral damage. There is rising evidence for a strong involvement of chemokines in postischemic BBB-breakdown. In a previous study, we showed that monocyte chemoattractant protein-1 (MCP-1)-deficiency results in a markedly reduced inflammatory reaction with decreased levels of interleukin-6, interleukin-1β, and granulocyte colony-stimulating factor after experimental stroke. With MCP-1 as one of the key players in stroke-induced inflammation, in this study, we investigated the influence of MCP-1 on poststroke BBB-disruption as well as transcription/translation of BBB-related genes/proteins after cerebral ischemia.
  
  
  METHODS
  Sixteen wild-type and 16 MCP-1(-/-) mice were subjected to 30 minutes of middle cerebral artery occlusion. By injecting high molecular-tracer, we compared the degree of BBB-disruption after middle cerebral artery occlusion. Real-time polymerase chain reactions and Western blot technique were used to compare tight-junction gene expression, protein secretion, and BBB-leakage.
  
  
  RESULTS
  Here, we report that MCP-1-deficiency results in a reduced BBB-leakage and a diminished expression of BBB-related genes occludin, zonula occludens-1, and zonula occludens-2. Real-time polymerase chain reactions and Western blot analysis revealed elevated claudin-5-levels in MCP-1(-/-) animals. MCP-1-deficiency resulted in reduced infarct sizes and an increased vascular accumulation of fluorescein-isothiocyanate-albumin.
  
  
  CONCLUSIONS
  The results of the study provide further insights into the molecular mechanisms of BBB-opening and may help to better understand the mechanisms of infarct development after cerebral ischemia.
authors.affiliation: Department of Neurology, University of Münster, Albert-Schweitzer Campus A1, Münster, Germany. strecker.jan@gmx.de
authors.forename: Jan-Kolja
authors.initials: JK
authors.lastname: Strecker
authors.forename: Jens
authors.initials: J
authors.lastname: Minnerup
authors.forename: Katharina
authors.initials: K
authors.lastname: Schütte-Nütgen
authors.forename: Burkhard
authors.initials: B
authors.lastname: Gess
authors.forename: Wolf-Rüdiger
authors.initials: WR
authors.lastname: Schäbitz
authors.forename: Matthias
authors.initials: M
authors.lastname: Schilling
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D018932:Chemokine CCL2 / Q000172:deficiency* / Q000235:genetics*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics; D020244:Infarction, Middle Cerebral Artery / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014176:Protein Biosynthesis / Q000235:genetics
chemical_list: D018932:Chemokine CCL2
keywords: CCL2, claudin-5; brain ischemia; brain-blood barrier; inflammation; occludin